CN105372343A - Method for separating and measuring substances related to memantine hydrochloride intermediate through gas chromatography - Google Patents
Method for separating and measuring substances related to memantine hydrochloride intermediate through gas chromatography Download PDFInfo
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- CN105372343A CN105372343A CN201510650689.7A CN201510650689A CN105372343A CN 105372343 A CN105372343 A CN 105372343A CN 201510650689 A CN201510650689 A CN 201510650689A CN 105372343 A CN105372343 A CN 105372343A
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- 239000000126 substance Substances 0.000 title description 41
- 238000000034 method Methods 0.000 title description 16
- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 title description 13
- 238000004817 gas chromatography Methods 0.000 title 1
- 229960000967 memantine hydrochloride Drugs 0.000 title 1
- CWNOIUTVJRWADX-UHFFFAOYSA-N 1,3-dimethyladamantane Chemical compound C1C(C2)CC3CC1(C)CC2(C)C3 CWNOIUTVJRWADX-UHFFFAOYSA-N 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000007789 gas Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 11
- 229960004640 memantine Drugs 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000012159 carrier gas Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012490 blank solution Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- -1 polysiloxane Polymers 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 238000003822 preparative gas chromatography Methods 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- MXAYGTASSPYUJB-UHFFFAOYSA-N 1-bromo-3-methyladamantane Chemical compound C1C(C2)CC3CC1(C)CC2(Br)C3 MXAYGTASSPYUJB-UHFFFAOYSA-N 0.000 description 1
- UZUCFTVAWGRMTQ-UHFFFAOYSA-N 1-methyladamantane Chemical compound C1C(C2)CC3CC2CC1(C)C3 UZUCFTVAWGRMTQ-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/025—Gas chromatography
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention belongs to the field of analytical chemistry and discloses a method for separating and measuring a memantine hydrochloride intermediate 1-Amino-3, 5-dimethyladamantane hydrochloride and substances related to the intermediate through the gas chromatography. According to the method, a nonpolar capillary chromatographic column of polysiloxane series and a hydrogen flame ionization detector are adopted, the content of the memantine hydrochloride intermediate and the content of the substances related to the memantine hydrochloride intermediate can be measured quantitatively, thereby the reactant purity in the memantine hydrochloride synthesis process can be effectively controlled, occurrence of side reactions and generation of impurities are reduced, and the product yield is raised. The method is great in specificity, high in accuracy and simple and convenient in operation.
Description
Technical field
The invention belongs to analytical chemistry field, be specifically related to the method for vapor-phase chromatography separation determination memantine intermediate and related substance thereof.
Background technology
Memantine is the noncompetitive glutamate receptor antagonists of a kind of voltage-dependent, moderate affinity, blocked glutamic acid concentration pathologic can raise the neure damage caused, be mainly used in middle severe Alzheimer Disease patient.Memantine chemistry 1-Amino-3,5-dimethyladamantanehydrochloride by name, molecular formula is C
12h
21nHCl.Memantine intermediated chemistry is called 1,3-Dimethyladamantane, and molecular formula is C
12h
20, structural formula is:
In the process of synthetic hydrochloric acid Memantine, need the purity controlling some important intermediate, with the generation of the generation and impurity that reduce subsidiary reaction, thus improve product yield and purity.For memantine intermediate 1-Amino-3,5-dimethyladamantanehydrochloride, need the related substance controlled to have 3, i.e. 1-Bromoaladamantane (related substance A), structural formula is:
1-Methyladamantane (related substance B), structural formula is:
1-Bromo-3-Methyladamantane (related substance C), structural formula is:
Impurity removal in memantine intermediate is incomplete, will affect pharmaceutical purity and quality.Therefore, realize separation determination memantine intermediate and related substance thereof, the purity of reactant in synthetic hydrochloric acid Memantine process can be ensured, reduce the generation of subsidiary reaction, improve product yield and purity, have important practical significance in the production and quality control thereof of memantine.
Summary of the invention
The object of the present invention is to provide a kind of analysis memantine intermediate 1-Amino-3, the purity of 5-dimethyladamantanehydrochloride and be separated the method for its related substance, thus realize the separated island form of memantine intermediate and its related substance, to ensure the purity of memantine intermediate, reduce the generation of subsidiary reaction, improve product yield.
A kind of method measuring memantine intermediate related substance of the present invention, is select suitable solvent by sample dissolution, adopts polysiloxane-based capillary chromatographic column;
Above-mentioned said solvent can be one or more in methyl alcohol, ethanol, normal hexane or methylene chloride.
Above-mentioned said chromatographic column is selected from the brands such as Agilent, OHIOVALLEY or SGE.
Above-mentioned said chromatographic column is nonpolar or the polysiloxane-based capillary chromatographic column of low pole.
Method of separating and assaying of the present invention, can realize in accordance with the following methods:
1) get memantine intermediate and related substance thereof appropriate, dissolved with solvent respectively, be mixed with the sample solution of the hydrochloric memantine intermediate of every 1mL and related substance 0.1 ~ 1.0mg thereof.
2) arranging injector temperature is 150 ~ 250 DEG C, flow rate of carrier gas is 1.0 ~ 3.0mL/min, programmed temperature method, heating schedule is initial temperature 120 DEG C, constant temperature 1 ~ 10min, with the heating rate to 200 DEG C of 5 ~ 10 DEG C per minute, constant temperature 6 ~ 20min, detector temperature is 220 ~ 320 DEG C, and split ratio is 1:1 ~ 50:1.
3) get 1) sample solution 1 ~ 5 μ L, inject gas chromatograph, completes the separation determination of memantine intermediate and related substance thereof.Wherein:
The model of gas chromatograph, has no special requirements, and the chromatograph that the present invention adopts is Agilent6890N gas chromatograph
Flame ionization ditector
Chromatographic column: DB-1 capillary chromatographic column (Agilent, 30m × 0.32mm, 5 μm);
Injector temperature: 200 DEG C;
Detector temperature: 250 DEG C;
Carrier gas (nitrogen) flow velocity: 2.4mL/min;
Split ratio: 5.0:1;
Sampling volume: 1 μ L
Column temperature rise program:
The present invention utilizes vapor-phase chromatography, adopt polysiloxane-based nonpolar capillary chromatographic column (30m × 0.32mm, 5 μm), can fast and effeciently separation determination memantine intermediate and related substance thereof, the invention solves the separation determination problem of memantine intermediate and related substance thereof, thus decrease the generation of synthetic hydrochloric acid Memantine subsidiary reaction and the yield of product, the results are shown in accompanying drawing 1 ~ 5.
Accompanying drawing explanation
The gas chromatogram of solvent (normal hexane) when Fig. 1 is embodiment 1;
Memantine intermediate and related substance gas chromatogram thereof when Fig. 2 is embodiment 1;
Memantine intermediate gas chromatogram when Fig. 3 is embodiment 1;
Memantine intermediate and related substance gas chromatogram thereof when Fig. 4 is embodiment 2;
Memantine intermediate and related substance gas chromatogram thereof when Fig. 5 is embodiment 3.
Embodiment:
Following examples are used for understanding the present invention further, but are not limited to the scope of this enforcement.Below by way of example forms, the assay of the memantine intermediate that the present invention relates to and related substance detection method thereof are described in further detail, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
Instrument and condition
Chromatograph: Agilent6890N gas chromatograph;
Detecting device: flame ionization ditector;
Chromatographic column: DB-1 capillary chromatographic column (Agilent, 30m × 0.32mm, 5 μm);
Injector temperature: 200 DEG C;
Detector temperature: 250 DEG C;
Carrier gas (nitrogen) flow velocity: 2.4mL/min;
Split ratio: 5.0:1;
Sampling volume: 1 μ L
Column temperature rise program:
Experimental procedure
Get memantine intermediate and related substance thereof appropriate, with n-hexane dissolution, be mixed with the solution of the hydrochloric memantine intermediate of every 1mL and each 1.0mg of related substance thereof.Get above-mentioned memantine intermediate and related substance solution thereof appropriate, be mixed with system suitability solution; Separately get normal hexane as blank solution.Analyze by above-mentioned chromatographic condition, record chromatogram.The results are shown in accompanying drawing 1 ~ 3, Fig. 1 is blank solution chromatogram; In Fig. 2, the chromatographic peak of retention time 11.889min is memantine intermediate, and all the other chromatographic peaks are the related substance of memantine.In Fig. 3, the chromatographic peak of retention time 11.886min is memantine intermediate.Fig. 1 ~ Fig. 3 shows: method of the present invention, effectively can be separated with its related substance by memantine intermediate, and can accurately quantitatively detect, to calculate the purity of memantine intermediate.
Embodiment 2
Instrument and condition
Chromatograph: Agilent6890N gas chromatograph;
Detecting device: flame ionization ditector;
Chromatographic column: DB-1 capillary chromatographic column (Agilent, 30m × 0.32mm, 5 μm);
Injector temperature: 205 DEG C;
Detector temperature: 250 DEG C;
Carrier gas (nitrogen) flow velocity: 2.4mL/min;
Split ratio: 5.0:1;
Sampling volume: 1 μ L
Column temperature rise program:
Experimental procedure
Get memantine intermediate and related substance thereof appropriate, with n-hexane dissolution, be mixed with the solution of the hydrochloric memantine intermediate of every 1mL and each 1.0mg of related substance thereof.Get above-mentioned memantine intermediate and related substance solution thereof appropriate, be mixed with system suitability solution; Separately get normal hexane as blank solution.By above-mentioned memantine intermediate and related substance mixed solution, blank solution inject gas chromatograph respectively, analyze by above-mentioned chromatographic condition, record chromatogram.The chromatographic peak that the results are shown in retention time 11.887min in accompanying drawing 4, Fig. 4 is memantine intermediate, and all the other chromatographic peaks are the related substance of memantine.
Embodiment 3
Instrument and condition
Instrument and condition
Chromatograph: Agilent6890N gas chromatograph;
Detecting device: flame ionization ditector;
Chromatographic column: DB-1 capillary chromatographic column (Agilent, 30m × 0.32mm, 5 μm);
Injector temperature: 200 DEG C;
Detector temperature: 250 DEG C;
Carrier gas (nitrogen) flow velocity: 2.3mL/min;
Split ratio: 5.0:1;
Sampling volume: 1 μ L
Column temperature rise program:
Experimental procedure
Get memantine intermediate and related substance thereof appropriate, with n-hexane dissolution, be mixed with the solution of the hydrochloric memantine intermediate of every 1mL and each 1.0mg of related substance thereof.Get above-mentioned memantine intermediate and related substance solution thereof appropriate, be mixed with system suitability solution; Separately get normal hexane as blank solution.By above-mentioned memantine intermediate and related substance mixed solution, blank solution inject gas chromatograph respectively, analyze by above-mentioned chromatographic condition, record chromatogram.The chromatographic peak that the results are shown in retention time 12.093min in accompanying drawing 5, Fig. 5 is memantine intermediate, and all the other chromatographic peaks are the related substance of memantine.
The following items of the present invention to described memantine intermediate and Related substance method thereof is verified:
System suitability is tested
Get memantine intermediate and related substance thereof appropriate, use n-hexane dissolution respectively, be mixed with the test liquid of hydrochloric memantine intermediate and related substance thereof.Gas chromatographic analysis is carried out, record chromatogram by the chromatographic condition of embodiment 1.As seen from Figure 2 this, between related substance and main peak, degree of separation meets the requirements with this understanding.
Sample introduction replica test
By memantine intermediate test liquid, by the chromatographic condition of embodiment 1, repeat sample introduction 6 times, the repeatability of investigation method.Can be added by result, the method sample introduction repeatability is good.
Stability of solution
Get the test liquid of memantine intermediate and related substance thereof, by the chromatographic condition of embodiment 1, respectively at sample introduction after 0,1,2,4,6 hour, stability of solution when investigating this product quantitative measurement, from result, this sample solution was stablized in 6 hours.
Durability
By fine setting injector temperature, flow rate of carrier gas and chromatographic column brand isochromatic spectrum condition, we have investigated the durability of method further.Found that, the method is to good tolerance under the condition such as chromatographic column, injector temperature change ± 5 DEG C, flow rate of carrier gas change ± 0.1mL/min of different brands.Under different brands chromatographic column, different injector temperature, flow rate of carrier gas condition, memantine intermediate and related substance retention time thereof without marked change, and all can reach effective separation.
Detectability
Get memantine intermediate and related substance thereof appropriate, accurately weighed, use n-hexane dissolution sample respectively, be mixed with the test liquid of response, then precision to measure test liquid appropriate, stepwise dilution, investigates by the chromatographic condition sample introduction of embodiment 1.Memantine intermediate detectability data are as shown in the table:
Claims (10)
1. vapor-phase chromatography is separated the method detecting memantine intermediate and related substance thereof, it is characterized in that: with suitable solvent by sample dissolution, adopt polysiloxane-based capillary chromatographic column, and flame ionization ditector detects.
2. method of separating and assaying according to claim 1, solvent can be one or more in methyl alcohol, ethanol, normal hexane or methylene chloride.
3. method of separating and assaying according to claim 1, chromatographic column is selected from the chromatographic column that brand is Agilent, OHIOVALLEY or SGE.
4. method of separating and assaying according to claim 1, chromatographic column is nonpolar or the polysiloxane-based capillary chromatographic column of low pole.
5. method of separating and assaying according to claim 1, is characterized in that, comprises following step:
1) get memantine intermediate and related substance thereof appropriate, dissolved with solvent respectively, be mixed with the sample solution of the hydrochloric memantine intermediate of every 1mL and related substance 0.1 ~ 1.0mg thereof.
6.2) arranging injector temperature is 150 ~ 250 DEG C, flow rate of carrier gas is 1.0 ~ 3.0mL/min, programmed temperature method, heating schedule is initial temperature 120 DEG C, constant temperature 1 ~ 10min, with the heating rate to 200 DEG C of 5 ~ 10 DEG C per minute, constant temperature 6 ~ 20min, detector temperature is 220 ~ 320 DEG C, and split ratio is 1:1 ~ 50:1.
7.3) get 1) sample solution 1 ~ 5 μ L, inject gas chromatograph, completes the separation determination of memantine intermediate and related substance thereof.
8. method for separating and analyzing according to claim 5, step 2) said carrier gas is nitrogen or helium.
9. method for separating and analyzing according to claim 5, step 2) said detector temperature preferably 250 DEG C.
10. method for separating and analyzing according to claim 5, step 2) said programmed temperature method, preferred following heating schedule:
。
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| Application Number | Priority Date | Filing Date | Title |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108918722A (en) * | 2018-08-02 | 2018-11-30 | 中国医科大学附属第医院 | A method of nmda receptor antagonist JCC-02 blood concentration is detected based on HPLC-MS/MS technology |
| CN116046926A (en) * | 2022-12-07 | 2023-05-02 | 合肥久诺医药科技有限公司 | A detection method for related substances of 1-bromo-3,5-dimethyladamantane |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102531919A (en) * | 2011-11-09 | 2012-07-04 | 广东肇庆星湖生物科技股份有限公司 | Preparation method of memantinehydrochloride |
| CN103483205A (en) * | 2013-10-12 | 2014-01-01 | 合肥久诺医药科技有限公司 | Preparation method of high-purity memantine hydrochloride |
| CN103524353A (en) * | 2013-10-12 | 2014-01-22 | 合肥久诺医药科技有限公司 | Preparation method for high-purity memantine hydrochloride |
-
2015
- 2015-10-09 CN CN201510650689.7A patent/CN105372343A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102531919A (en) * | 2011-11-09 | 2012-07-04 | 广东肇庆星湖生物科技股份有限公司 | Preparation method of memantinehydrochloride |
| CN103483205A (en) * | 2013-10-12 | 2014-01-01 | 合肥久诺医药科技有限公司 | Preparation method of high-purity memantine hydrochloride |
| CN103524353A (en) * | 2013-10-12 | 2014-01-22 | 合肥久诺医药科技有限公司 | Preparation method for high-purity memantine hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| LITI GRICE，ET AL: "Diamondoid hydrocarbon ratios as indicators of biodegradation in Australian crude oils", 《ORGANIC GEOCHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108918722A (en) * | 2018-08-02 | 2018-11-30 | 中国医科大学附属第医院 | A method of nmda receptor antagonist JCC-02 blood concentration is detected based on HPLC-MS/MS technology |
| CN108918722B (en) * | 2018-08-02 | 2021-04-23 | 中国医科大学附属第一医院 | A method for detecting the blood concentration of NMDA receptor antagonist JCC-02 based on HPLC-MS/MS technology |
| CN116046926A (en) * | 2022-12-07 | 2023-05-02 | 合肥久诺医药科技有限公司 | A detection method for related substances of 1-bromo-3,5-dimethyladamantane |
| CN116046926B (en) * | 2022-12-07 | 2024-11-05 | 合肥久诺医药科技有限公司 | Detection method of 1-bromo-3, 5-dimethyl adamantane related substances |
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